Poly(alkyl‐terphenyl piperidinium) membranes and ionomers display outstanding hydrogen‐barrier properties and mechanical properties as well as excellent hydroxide‐ion conductivity that results in an excellent power density of 2.58 W cm⁻² and 1.38 W cm⁻² at 80 °C in H₂/O₂ and H₂/air, respectively, along with a new, outstanding specific power in alkaline‐exchange‐membrane fuel cells.

Structurally characterizing new and poorly crystalline materials such as covalent organic frameworks is highly challenging. The dynamic protocol of this work overcomes this challenge through a systematic likelihood ordering based on intuitive heuristics and X‐ray diffraction patterns. It succeeds in unambiguously identifying a material's atomic‐level structure, accounting for the operando conditions and inherent temporal character of experiments.

The internal structure of single‐chain nanoparticles (SCNPs) has been investigated, forming nanosized domains preformed during the crosslinking process. We present proof for the presence of nano‐compartments within SCNPs via a combination of electron paramagnetic resonance (EPR) and fluorescence spectroscopy. A novel strategy to encapsulate labels within such water dispersible SCNPs is presented.

The kinetics of E. coli bacterioferritin di‐ferrous ferroxidase centre reacting with O₂ and H₂O₂ shows that H₂O₂ reacts circa 1000 times faster than O₂ implying that the primary in vivo role of the protein is ROS detoxification rather than iron sequestering.

We examined thousands of common materials in two widely used computation‐ready metal–organic framework databases (MOF DBs) to reveal how structural discrepancies affect simulated CH₄, H₂, CO₂ uptakes and CH₄/H₂ separation performances of MOFs. Identification of the top‐performing materials for gas separation was shown to strongly depend on the DB used in simulations.

High‐silica CHA zeolite membranes show ultra‐high Kr/Xe selectivity and superior hydrothermal stability. Together with their irradiation stability, high‐silica CHA zeolite membranes can pave the way to enrich radioactive ⁸⁵Kr from xenon for a notable decrease in the volatile nuclear waste volume.

The highly diastereoselective Fe‐catalyzed anaerobic Markovnikov‐selective hydration of alkenes using nitroarenes as oxygenation reagents is reported.

A screening yields the first non‐carbohydrate small molecules mimicking the interaction of carbohydrates in the binding sites of bacterial lectins. The catechols, known as PAINS, were carefully validated in numerous biophysical assays. A crystal structure in complex with Pseudomonas aeruginosa LecA and NMR analyses with mammalian C‐type lectin Langerin prove the catechol moiety as a general replacement motif for carbohydrates in calcium(II)‐binding lectins.

Objective

Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease of unknown etiology. Although the prevalent view regards a CD4⁺‐lymphocyte autoimmune reaction against myelin at the root of the disease, recent studies propose autoimmunity as a secondary reaction to idiopathic brain damage. To gain knowledge about this possibility we investigated the presence of axonal and myelinic morphological alterations, which could implicate imbalance of axon‐myelin units as primary event in MS pathogenesis.

From a library of 26 deoxyuridine‐ and deoxycytidine‐derived diarylethenes we identified two high‐performance photoswitches with near‐quantitative, fully reversible back‐and‐forth switching, high reaction quantum yields and no detectable thermal or photochemical deterioration. Incorporated into an oligonucleotide, these nucleotides allowed the optochemical modulation of the activity of T7 RNA polymerase.

Genetic activation artificially induced a plasmid‐encoded natural product biosynthetic gene cluster and activated the complex biosynthesis of a previously unknown cytotoxin named sandarazol. Its biosynthesis is unique in featuring the genetic blueprint for the formation of intriguing structural features such as an α‐chlorinated ketone, an epoxyketone, and a rare (2R)‐2‐amino‐3‐(N,N‐dimethylamino)‐propionic acid building block.

A new series of discrete oligomeric linearly fused polycyclic aromatic hydrocarbons (PAHs) stabilized by peri‐annulation in described. The intrinsic perylene units of the novel PAHs with up to 13(!) linearly fused rings are responsible for colorful and bright photophysical properties.

Background

We describe a 4‐generation Dutch pedigree with a unique dominantly inherited clinical phenotype of a combined progressive chorea and cervical dystonia carrying a novel heterozygous dopamine D2 receptor (DRD2) variant.

Bifunctional hypervalent iodine reagents for two‐component cysteine‐cysteine and cysteine‐lysine stapling are reported. Efficient and selective stapling on non‐protected peptides was observed, and post‐stapling modification could be easily achieved using reactive esters or cycloaddition on the thioalkynes formed on the cysteine residue. One stapled peptide displayed both enhanced helicity and binding to the MDM2 protein.

Efficient intracellular delivery of synthetic native proteins is a challenge due to endosomal entrapment and subsequent degradation. We report the enhanced cellular uptake of fluorescently labelled synthetic proteins by attaching a newly developed cell‐penetrating peptide (CPP) composed of cyclic deca‐arginine linked to DABCYL.

Dozens of macrolide antibiotics are known that differ from each other only in the decoration of an otherwise highly conserved 16‐membered lactone core and in the lateral glycosylation pattern. A unified approach was explored that holds the promise of bringing numerous members of this type into reach from a single “eastern” building block.

A B‐Cu gas diffusion electrode (GDE) system was developed for highly selective CO₂ conversion to C₂₊ products at high relevant current densities by mitigating the flooding problem and tuning the three‐phase boundary. Anodic protection by sacrificial Zn nanosheets remarkably improved the long‐term stability for CO₂ electroreduction at high current densities.

Cu₂O nanocubes showed a remarkable increase (30 %) in the Faradaic efficiency for C₂₊ liquid products after the decoration with Ag nanoparticles. Operando spectroscopy revealed a reaction‐driven redispersion of Ag on CuO_x as well as a certain Cu–Ag miscibility. These changes were coupled with significant variations in the binding of CO to Cu that favored the enhancement of the liquid product yields.

One sugar has to be attached before the transannular ketone is revealed from an alkyne precursor to render the first successful total synthesis ever of a member of the aldgamycin family of antibiotics. Although this phasing of events implies that the precious branched monosaccharide must be carried through several steps, a practical and scalable synthesis of the required aldgarose fragment greatly mitigates the “cost” of this strategy.

Background

Nilotinib is US Food and Drug Administration–approved for leukemia, and this open‐label study investigated the safety, tolerability, and potential clinical effects of nilotinib in medically optimized patients with Parkinson's disease.

Objective

The role of the survival of motor neuron (SMN) gene in amyotrophic lateral sclerosis (ALS) is unclear, with several conflicting reports. A decisive result on this topic is needed, given that treatment options are available now for SMN deficiency.

Surprisingly, large peptides (Protamine, 5.1 kDa) can permeate through bacterial outer membrane channels. The use of fluorescence, electrophysiology, and all‐atom modeling allows to quantify the flux. This approach can be transferred to related problems.

New materials can be created without the need to follow conventional criteria and routes to synthesis. We demonstrate this for Ge–Sn, a system actively investigated for optoelectronic applications to overcome conventional cubic Si's deficiencies. Ge and Sn are however unreactive in the bulk, but we remove reactivity barriers and form a different structure, a simple new cubic solid solution.

PEPSTAR, a “rising star” in peptide synthesis, features a “nanostar” support to grow peptides with organic solvent nanofiltration for isolation. The three‐armed and monodisperse nanostar enables efficient nanofiltration and real‐time reaction monitoring. A cycle consists of coupling, Fmoc removal and nanofiltration, which all performed continuously in a synthesizer to produce high purity peptide crudes through a one‐pot approach.

Background

No clinical trials have been specifically designed to compare medical treatments after surgery in Parkinson's disease (PD).

AsqJ catalyzes a complex rearrangement sequence in quinolone biosynthesis. We show the AsqJ biocatalytic potential to significantly exceed this natural function. An unprecedented reaction pathway leading to quinazolinones is uncovered, functionally and mechanistically characterized in detail, revealing a unique substrate‐dependent product selectivity in enzyme catalysis.

Highly selective chiral self‐sorting. The chiral self‐sorting behavior of large cubic [8+12] salicylimine cage compounds was investigated, revealing a high selectivity for the most symmetric cage compounds, for which an explanation is presented. The properties of the isolated enantiopure and meso cage compounds were investigated by single crystal X‐ray diffraction and gas sorption measurements showing high porosities and selectivities.

A detection system was devised to screen dehydrogenase enzymes (DH) at ultrahigh‐throughput in in vitro droplet compartments. An NAD(H) analogue and a DH DNA library were co‐immobilised on beads. Water‐in‐oil emulsion droplets containing cell‐free expression mix and substrate allow compartmentalised protein production and catalysis. A fluorescent sensor of NAD(H) redox state was loaded onto beads, allowing bulk sorting of 2×10⁴ DH variants in a day by flow cytometry.

Direct and selective sp³ C−H chlorination has been achieved using a photoinduced strategy. This approach is based on a radical‐chain propagation that exploits the ability of aminium radicals to undergo site‐selective H‐atom transfer (HAT).

The reaction kinetics of H‐atom transfer mediated by iron(IV)oxo complexes with different cis‐ligands can be studied in a modular flow reactor coupled to MS detection. The HAT reactivity correlates with the intrinsic properties of the isolated complexes in the gas phase. A ligand with a larger binding energy forms a more reactive complex for the HAT reactions, has a weaker Fe^IV=O bond, and forms a stronger Fe^IIIO−H bond after the HAT reaction.

An approach to the catalytic dehydrogenation of alkanes and heterocycles uses Ru and redox‐active ligands. A wide range of functionalized substrates afforded dehydrogenated products in good yields. Preliminary mechanistic studies suggest that a redox‐active ligand‐assisted intermolecular hydrogen atom transfer is crucial to this process.

The nitridogermanates(III), Ca₆[Ge₂N₆] and Sr₆[Ge₂N₆], contain the hitherto unknown molecular anion [Ge₂N₆]¹²⁻ featuring a Ge−Ge‐bond and thus represent the first members of a novel class of compounds virtually unknown in the nitride chemistry of tetrel elements.

Cu(OTf)₂ promotes the oxidative arylation of nitriles and N‐heterocycles to generate ionic products. Mechanistic studies suggest the process operates via reductive elimination from a Cu^III complex bearing neutral N‐ligands to generate nitrilium and pyridinium products. The reaction is general for a range of N(sp) and N(sp²) precursors and can be applied to drug synthesis and late‐stage N‐arylation.

Multivalent interactions mediated by the cellular glycocalix are ubiquitous in biological processes. We utilized glycodendrimersomes, a type of synthetic cell membrane mimic to probe the carbohydrate biological activity towards lectins. We demonstrated that mannose could organize the sugar moieties into periodic nanoarrays resulting in a new effective ligand yielding a ten‐fold increase in the kinetic and thermodynamic constant of association.

Solid‐state filling of a stable phosphorus ylid open‐cage fullerene is followed by heating, inducing an in situ intramolecular Wittig reaction to reduce the size of the cage opening and trapping a single gas atom or molecule inside. Expensive gases can be compressed to high pressure, leading to high incorporation of the endohedral species. Cage closure steps allow preparation of gram‐scale endohedral fullerenes including ³He@C₆₀, HD@C₆₀, and Ne@C₆₀.

A picky ligand: A chiral phenanthroline ligand allows for the site‐ and enantioselective imidation (Ns=para‐nitrosulfonyl) of a variety of sulfides. Silver acts in concert with an achiral 1,10‐phenanthroline (1,10‐phen) ligand as the catalytically active center.

KrF₂ and [XeF₅][AsF₆] react in anhydrous HF to form [F₅Xe(FKrF)AsF₆] and [F₅Xe(FKrF)₂AsF₆]. The complexes were structurally characterized by low‐temperature single‐crystal X‐ray diffraction and Raman spectroscopy. The KrF₂ ligands interact with xenon(VI) through Xe‐ ‐ ‐FKrF secondary bonds that are shown by computational studies to be noncovalent, electrostatic, σ‐hole interactions. The complexes provide unique examples of mixed noble‐gas compounds.

Using quasi‐elastic neutron scattering (QENS), the mobility of water molecules confined in the premelting layer of three different ice/clay nanocomposites is quantified. Layers of low‐density liquid water are formed adjacent to ice Ih and clay mineral interfaces. This leads to a reduction of the translational diffusion coefficient within the premelting layer.

By exploiting the dynamic chirality, directionality of motion and shape change of a single light‐driven motor embedded in a liquid‐crystal network, complex mechanical motions including bending, walking and helical motion, in soft polymer materials are achieved which offers fascinating opportunities toward inherently photo‐responsive materials.

A resplendent trio: Protic ionic liquids (PILs) with nucleophilic anions served in concert as regenerable reaction medium, Brønsted acid, and a source of nucleophile. Heating of donor–acceptor cyclopropanes with 1‐methylimidazolium thiocyanate (B:⋅HNCS) afforded products of formal (3+2)‐ and (4+2)‐cycloaddition of isothiocyanic acid.

Moving past classical passive responsive behavior, transient volume phase transitions of poly(methacrylic acid) microgels can be achieved through the use of a chemical fuel. The deswelling creates a transient hydrophobic environment with a lifetime tunable via pH and fuel concentration with possible applications for encapsulation/release.

The right combination: An artificial enzyme combination is presented that continuously produces NAD⁺ from oxygen and water and a catalytic amount of pyruvate, without additional substrates and without generating byproducts. Three enzymes are covalently encapsulated into a substrate‐permeable silica nanoreactor by a mild fluoride‐catalyzed sol–gel process. NAD⁺ from the nanoreactors was successfully used for the continuous production of NAD⁺ for sensing glucose and for rapidly reducing the non‐oxygen binding methemoglobin to oxygen‐binding hemoglobin.

A conductive polymer (PEDOT:PSS) and potassium poly(heptazine imide) (K‐PHI) are combined in one hybrid nanocomposite as electron donor and photocatalyst, respectively. The composite represents an example of unconventional photocatalysis: K‐PHI modulates the physicochemical properties of the conductive polymer upon exposure to light and dark in different environments.

Temperature is a clinical marker for tissue metabolism and can be used for the detection of diseases. Besides intrinsic magnetic resonance (MR) methods for relative temperature changes, there are only limited methods for absolute temperature imaging. In this study we present an in vitro method with a photoswitchable contrast agent for absolute and concentration independent 3D temperature imaging.

Process analytical technologies hold tremendous promise in multistep continuous flow synthesis. Here, four orthogonal real‐time analytical tools are employed in a three step synthesis, with phase separations. Advanced data processing techniques, such as indirect hard modeling and deep learning, facilitate quantification of up to 9 process components. These analytical capabilities are demonstrated for both steady state and dynamic experiments.

Background

VPS35 is part of the retromer complex and is responsible for the trafficking and recycling of proteins implicated in autophagy and lysosomal degradation, but also takes part in the degradation of mitochondrial proteins via mitochondria‐derived vesicles. The p.D620N mutation of VPS35 causes an autosomal‐dominant form of Parkinson's disease (PD), clinically representing typical PD.

Only very recently has it become possible to obtain accurate melting and boiling points from quantum‐chemical simulations. These show that the periodic trends observed for the Group 12 elements are exclusively relativistic in nature, which can be rationalized in terms of the relativistic change in the corresponding cohesive energies.

An in situ technique is presented that closes the gap between catalyst degradation studies in real devices and fundamental electrochemical analyses. The method involves direct measurement of platinum dissolution in realistic catalyst layers and through Nafion membranes. The impact of catalyst loading and electrode–electrolyte interface on platinum dissolution, as well as transport behavior of dissolved Pt species through Nafion membranes, are investigated.

Background

Gait disturbance is an early, disabling feature of Parkinson's disease (PD) that is typically refractory to dopaminergic medication. The cortical cholinergic system, originating in the nucleus basalis of Meynert of the basal forebrain, has been implicated. However, it is not known if degeneration in this region relates to a worsening of disease‐specific gait impairment.

March Infographic: Cholinergic Basal Forebrain Volumes Predict Gait Decline in Parkinson's Disease

Objective

Diagnosing autoimmune encephalitis (AIE) is difficult in patients with less fulminant diseases such as epilepsy. However, recognition is important, as patients require immunotherapy. This study aims to identify antibodies in patients with focal epilepsy of unknown etiology, and to create a score to preselect patients requiring testing.

Background

High‐frequency thalamic stimulation is an effective therapy for essential tremor, which mainly affects voluntary movements and/or sustained postures. However, continuous stimulation may deliver unnecessary current to the brain due to the intermittent nature of the tremor.

Copper catalyst for electrochemical CO₂ conversion has been unraveled in situ down to the atomic scale using electrochemical atomic force microscopy under highly gas‐evolving reaction conditions. Oxidized copper surfaces enter different morphological regimes in cathodic potential ranges down to −1.1 V_RHE coupled with surface reconstructions and varying density of undercoordinated reaction sites.

Chemical reaction networks based on antagonistic enzymes can show new behaviour when the enzymes are immobilized into layered compartments to impose spatial diffusive constraints. This allows to overcome mismatches of the enzymatic activities and reduces crosstalk in their pH‐dependent activity when targeting pH‐feedback mechanisms to program self‐assembly lifecycles.

High‐resolution cryo‐EM structures of nanodisc‐embedded Ca_v1.1 in complex with antagonists Levamlodipine, (R)‐(+)‐Bay K8644, and dual agonist/antagonist (S)‐(−)‐Bay K8644 reveal the molecular basis of the allosteric modulation of the voltage‐gated Ca²⁺ channel Ca_v1.1 by dihydropyridine (DHP) drugs. Advanced structural understanding of the stereo‐selective mode of action of DHP will facilitate drug discovery targeting Ca_v channels.

Hydrogels adapt to different colors of light: This study introduces how the mechanical properties of photo‐dynamic hydrogels precisely and reversibly adapt to light of different wavelengths by engineering photo‐switchable multivalency effects in star polymer networks.

Using spectroscopic, structural, and quantum‐chemical methods, a heterocyclic compound containing the alkaline earth metal beryllium was characterized, which exhibits significant antiaromaticity. This species was subjected to chemical reduction and Lewis base coordination.

The van der Waals stabilization of transition states in smaller‐pore MFI zeolites makes secondary alcohols, 3‐heptanol, and 2‐methyl‐3‐hexanol more reactive toward hydronium ion catalyzed elimination than in the sterically larger pore BEA zeolite. Whereas the stabilization of the C_β‐H transition state provided by intraporous alcohol for 2‐methyl‐2‐hexanol provides an additional stabilization in the sterically larger pore BEA zeolite, making hydronium ions in BEA more reactive than in MFI.

Amyloid fibrils preferentially originate from the surface of existing fibrils, as the fibril surface catalyzes the conversion of monomeric precursors in a process called secondary nucleation. Metastable protofibrils, an alternative, particularly toxic, assembly type of amyloid proteins, bind amyloid fibril surfaces and obstruct secondary nucleation. Protofibrils thereby delay their own replacement by amyloid fibrils.

Closthioamide is a symmetric perthioamidated nonribosomal peptide (NRP) produced by an atypical NRP‐synthetase‐independent biosynthetic pathway. Using a combination of genome editing and in vitro biochemical assays, we elucidated the last steps of closthioamide biosynthesis and found an unexpected asymmetrical route involving novel enzyme functions for members of the aldo‐keto reductase and transglutaminase protein families.

Based upon precise terahertz (THz) measurements of the solvated amino acid glycine and accompanying ab‐initio molecular‐dynamics simulations, it is shown that the N‐C‐C‐O open/close mode at 315 cm⁻¹ serves as a sensitive, label‐free probe for the local protonation of the amide group.

Dynamic evolution of active sites and key oxygen intermediate products during the ORR and OER on N‐doped carbon catalysts are monitored experimentally with in situ ATR‐IR spectra. With the assistance of isotopic labeling, the formation of *OOH species from O₂ ⁻* (O₂ ⁻*+H₂O→OOH*+OH⁻) is suggested to be a possible RDS during the ORR process, whereas the generation of O₂ from OOH* species is the most possible RDS during the OER process.

The first parent arsanylalanes and ‐gallanes stabilized only by a Lewis base were synthesized. These compounds are accessible via a salt metathesis reaction of LB⋅E′H₂Cl and KAsH₂ and a H₂ elimination reaction between LB⋅E′H₃ and AsH₃, respectively. In addition, the unprecedented branched compounds IDipp⋅E′H(EH₂)₂ (E′=Al, Ga; E=As, P could be obtained.

Configurationally stable and flexible organoboron helicenes consisting of either all‐ortho‐fused or a combination of angularly and linearly fused rings were synthesized by a modular approach from small achiral building blocks. A concept towards extended organoboron helices comprising both types of helically chiral compounds as primary substructures is presented.

Just a pinch of Ba metal: Efficient hydrogenation of a wide range of substrates is achieved with metallic barium previously activated by metal vapor synthesis. A mechanism in which Ba⁰ and BaH₂ are both essential is discussed.

Length and pathway control of BODIPY‐based supramolecular polymers in aqueous media has been achieved by programmable hydrogen bonding (intra‐ vs. intermolecular) using a new N‐(2‐hydroxyethyl)amide supramolecular synthon as a hydrogen bonding lock. These findings open up new directions in the field of controlled supramolecular polymerization.

RNA‐PROTACs are new chimeric structures that mediate the proteasomal degradation of RNA‐binding proteins (RBP). They comprise an E3‐recruiting peptide conjugated to a short modified RNA, which is iso‐sequential with the native binding element to which the RBP binds in cells. RNA‐PROTACs offer a fast, rational and general approach to target an entire class of protein (RBPs) that has proven difficult until today to target pharmacologically.

The first three examples of neutral palladium‐oxo clusters (POCs), Pd₁₆, Pd₁₆Cl, and Pd₂₄, were prepared by simple open‐pot, room‐temperature reactions of palladium(II) salts in sodium dimethylarsinate aqueous solutions. The dimethylarsinate capping groups act as bidentate, monoanionic ligands for the various palladium‐oxo cores. The three POCs were fully characterized in the solid, solution, and gaseous states by a multitude of physicochemical techniques.

Negatively charged electron acceptors and auxochromes? New sulfonamides make it possible! 1‐Aminopyrenes decorated with the new sulfonamides had low m/z ratios and high mobility in an electric field. Their glycoconjugates with reducing sugars were separated and detected at sub‐picomolar concentration by multicolor emission in a DNA analyzer (see picture).

Objective

Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants.

A deceptively simple proton abstraction from nickel‐bound formate not only prepares the resulting CO₂ ²⁻ unit for the release of CO in contact with electrophiles but opens up unique complex reaction schemes including reduction of nickel(II) to nickel(I) and coupling of CO₂ units to give oxalate and mesoxalate. Mesoxalate formation from individual CO₂ units is so far unprecedented.

Bioengineered protein fibers were prepared through electrostatic complexation of a positively charged polypeptide and a negatively charged azobenzene‐based surfactant. The photo‐isomerization of the azobenzene moiety from E‐ to Z‐isomer reversibly triggered a modulation of the bulk protein fiber's mechanical performance.

C(sp³)−H bonds have been converted to cyano derivatives under metal‐ and cyanide‐free condition in the presence of visible light and an organic dye. Potential applications of this method in the late‐stage transformation of complex drug molecules, steroid derivatives, and gram‐scale reactions have been described.

Electron paramagnetic resonance spectroscopy reveals that the final metastable catalytic state (S₃) in biological water oxidation in higher plants is a mixture of a high‐spin and an intermediate‐spin form. These two forms represent distinct structural components related to water binding and activation on the path towards oxygen evolution.

Snapshots from femtosecond mid‐infrared laser spectroscopy reveal spin‐dependent formation of different binding modes of carbon dioxide to a transition‐metal center. The ultrafast excitation of an iron(III) oxalate precursor complex with ultraviolet pulses releases a neutral carbon dioxide molecule within 500 fs and generates a nascent iron‐CO₂‐primary complex that isomerizes on a picosecond time scale.

Extremely soft temperature‐sensitive nanogels adsorbed to the solid/water interface were studied by atomic force microscopy. The ultra‐soft nanogels disappeared in the classical 2D height image. By detailed analysis of Force Volume data the extraordinary disk‐like and entirely homogeneous but extremely soft structure of the nanogels was resolved.

A novel neuroprotective compound, SB1617, was developed via phenotypic assay by image‐based monitoring of tau protein aggregation. Label‐free target identification study revealed that SB1617 inhibits PDIA3 and DNAJC3, thereby regulates tau proteostasis through the activation of PERK signaling pathway in a stress‐responsive manner. The administration of SB1617 showed neuroprotective effects in mice with tauopathy involving ER stress.

Objective

Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA.

The phenomenon selective interfacial accumulation (SIA) is reported for an aqueous system. Based on interfacial migration, kinetic control and capture of the spatial organisation in a variety of compartmentalized macroscopic structures, without the need to create barrier layers between compartments, is possible. SIA opens an avenue for 3D phase separation approaches towards synthetic compartmentalized systems, and it is also relevant to understanding and mimicking intracellular organisation.

Halide abstraction of L(X)GaP(^MecAAC) yielded [LGaP(^MecAAC][An] (An=B{C₆H₃(CF₃)₂}₄; B(C₆F₅)₄; Al{OC(CF₃)₃}₄). The cations not only show substantial Ga−P π‐bonding contribution but can also be regarded as heteroallyl cations according to quantum chemical calculations, since the positive charge is shifted via mesomerism.

Background

Deficits in maintaining and manipulating sequential information online can occur even in patients with mild Parkinson's disease. The subthalamic nucleus may play a modulatory role in the neural system for sequential working memory, which also includes the lateral prefrontal cortex.

Highly reactive dinickel(I) complexes with an open cleft between two “T”‐shaped metalloradicals are accessible via H₂ release from a dinickel(II) dihydride complex based on a pyrazolate/β‐diketiminato hybrid ligand. The barrier to intramolecular H₂ elimination is drastically lowered by protonation at the ligand periphery.

DNA nanotechnology can be used to rationally design a molecular gate to control the transport of small‐molecule drugs across bilayer membranes. The DNA pore with a thrombin‐binding aptamer lid opens in the presence of thrombin to increase the transport of the cytotoxic drug topotecan by 330‐fold. The nanodevice could be adapted for a range of different protein triggers with applications in biosensing, research, and biomedicine.

Objective

This study was undertaken to determine whether a low residual quantity of dystrophin protein is associated with delayed clinical milestones in patients with DMD mutations.

Objective

A study was undertaken to assess whether cerebral small vessel disease (SVD) computed tomographic (CT) biomarkers are associated with long‐term outcome after intracerebral hemorrhage.

Background

Commentators suggest that patients have unrealistic expectations about the pace of research advances and that such expectations interfere with patient decision‐making.

Background

Orthostatic hypotension is common in patients with Parkinson's disease (PD). However, it remains unknown whether orthostatic hypotension is a marker of prodromal PD or more advanced disease. The objectives of this study were to assess whether orthostatic hypotension is a prodromal marker of PD in the general population.

Unprecedent structural details of the glycans of the RBD of SARS‐CoV‐2 spike glycoprotein have been revealed by NMR spectroscopy. Unexpected and non‐previously reported glycoepitopes have been detected. The interaction of the RBD glycoprotein with diverse human lectins has been scrutinised by exploiting the NMR signature of the ¹³C‐glycans. Our analysis permitted to identify the corresponding glycan epitopes responsible for the interaction with each lectin.

Background

X‐linked dystonia‐parkinsonism is a rare neurological disease endemic to the Philippines. Dystonic symptoms appear in males at the mean age of 40 years and progress to parkinsonism with degenerative pathology in the striatum. A retrotransposon inserted in intron 32 of the TAF1 gene leads to alternative splicing in the region and a reduction of the full‐length mRNA transcript.

A host–guest complex self‐assembled through Co²⁺ and cucurbit[5]uril (Co@CB[5]) is used as a supramolecular catalyst on the surface of metal oxides including porous indium tin oxide (ITO) and porous BiVO₄ for efficient electrochemical and photoelectrochemical water oxidation.

All in one: Highly efficient multisegment native chemical ligation (NCL) has been developed by exploiting the Fmoc group to temporarily mask the N‐terminal Cys of the peptide thioester fragments. Fmoc removal and NCL are achieved in the same reaction mixture through pH adjustments in presence of 20 % piperidine. The simplicity and inherent robustness of this method make it an attractive approach for the high‐yielding total synthesis of proteins.

Metal vinyl carbenes generated by retro‐Buchner reaction or an enyne cycloisomerization cascade react with 1,3‐dienes to afford complex 1,4‐cycloheptadienes in a formal (4+3) cycloaddition process. A combination of experiments and computations provides a full mechanistic picture in which two pathways, a vinylcyclopropanation/Cope rearrangement or a non‐concerted (4+3) cycloaddition, can compete depending on the substitution pattern of the substrate.

Potent bicyclic peptide inhibitors of the RbAp48‐MTA1 interaction were developed by structure based stepwise optimization of the cyclization linker. The strategy exemplifies design of peptide derived inhibitors of protein–protein interactions involving large surface areas.

Towards the development of improved biophotovoltaic devices for solar energy conversion, a mixed monolayer constituted by photosystem I trimers and monomers enables the fabrication of highly efficient biophotoelectrodes by minimizing electronic short‐circuiting processes while at the same time ensuring a high density of photoactive molecules per unit area.

Background

It is unknown whether individuals with tic disorders are at increased risk for serious transport accidents.

The N ⁶‐methyladenosine (m⁶A) methyltransferase METTL3‐METTL14 shows remarkable cosubstrate promiscuity, enabling sequence‐specific internal labeling of RNA. The transfer of ortho‐nitrobenzyl and 6‐nitropiperonyl groups allows enzymatic photocaging of RNA. METTL16 is less promiscuous but suitable for chemo‐enzymatic labeling via click chemistry. Since both enzymes act on distinct sequence motifs, their combination enables the modification of different sites in a single RNA.

Readily available thiols are chemoselectively converted to valuable unprotected sulfinamides using an inexpensive iron catalyst through the formation of two distinct new bonds (S=O and S−N) in a single step. A hydroxylamine‐derived reagent acts as dual oxidant and amino group donor for the synthesis of structurally and functionally complex sulfinamides.

Whereas in conventional organolithium chemistry unsolvated dimers are generally more stable than solvated monomers and their sodium and potassium analogues are less stable still, curiously this trend seems to be reversed in carbenoid systems. DOSY‐NMR, SC‐XRD analyses and computational studies on a chiral test system show dramatic changes in the stability depending on the solvent and the formed structures.

C−N isomerization reactions on borate‐based anionic bi‐mesoionic carbene ligands are reported. The Co^II complexes with these ligands display geometries, spin states, and reactivities that are controlled by agostic interactions in the secondary coordination sphere.

New bis‐ and mono‐ tropolono‐ and benzo‐pyranyl humulene meroterpenoids, priviledged structures with diverse potent bioactivities, were synthesised using a rational synthetic biology platform based on the heterologous expression of genes from three different natural product pathways in the fungal host Aspergillus oryzae. Control over number of additions to humulene, ring contractions and humulene hydroxylation was achieved.

Background

Multiple system atrophy (MSA) is a rare neurodegenerative disorder, and its parkinsonian variant can be difficult to delineate from Parkinson's disease (PD). Despite laryngeal dysfunction being associated with decreased life expectancy and quality of life, systematic assessments of laryngeal dysfunction in large cohorts are missing.

Terphenyl biradicals are generated from iodinated precursors en route by deposition through the reactive drift tube of a newly devised radical deposition source. Upon deposition onto iodine‐passivated metal surfaces, the terphenyl radicals self‐assemble into ordered structures but remain active for C−C coupling into dimers and extended oligomers.

Novel Diels–Alder polymer networks with tunable aggregation‐induced emission (AIE) behavior, constructed from non‐emission dimaleimide‐substituted tetraphenylethene and linear furan‐based copolymers, have a tunable fluorescent “turn on/off” property, which shows an accurate response to temperature.

To gain insight into the nonlinear optical properties and reactivity of organotetrel chalcogenide clusters, we studied the silicon homologues, [(RSi)₄S₆] (R=Ph, Np, Sty), and their products upon reaction with [AuCl(PPh₃)], [{RSi(μ‐S)}₂{AuPPh₃(μ‐S)}₂]. Quantum chemical studies of cluster dimers elucidated the differences in the habit of silicon and tin compounds, and DFT calculations of crystalline models confirmed the applicability of these methods.

Metal‐free electrocatalyzed B−H nitrogenation is used to synthesize various N‐heterocyclic nido‐carboranes.

Objective

To determine the clinical and molecular features in patients with amyotrophic lateral sclerosis 4 (ALS4) due to mutations in the senataxin (SETX) gene and to develop tools for evaluating SETX variants.

The dehydration of n‐octanaloxime to n‐octanenitrile catalysed by an aldoxime dehydratase (OxdB) overexpressed in E. coli is carried out in Pickering emulsions stabilised solely with silica particles of different hydrophobicity. The effects of particle wettability and particle concentration are evaluated with respect to the conversion of the reaction.

RNA aptamers find increasing application in synthetic biology as exogenous gene control elements, but high‐resolution structural characterization in vivo is challenging. We report here the NMR‐spectroscopic observation of ligand binding by the 2′‐deoxyguanosine riboswitch aptamer in eukaryotic cells and show that the binding mode established by in vitro characterization of this aptamer is maintained in eukaryotic cellular environment.

Herein we disclose the on‐surface redox coupling of arylamines and nitroarenes on Ag(111). Starting from well‐designed monomeric precursors, the cross‐coupling yielding azo bridged polyphenylenes was investigated by STM and XPS. Further, first steps toward copolymerization were performed with two comonomers. Mechanistic studies and supportive DFT calculations are provided.

Iron‐silica membranes grown from laboratory and natural solutions are made of iron nanoparticles over amorphous silica, similar to a heterogeneous catalyst, and under geochemically plausible conditions they show a bilayer structure. These results provide a mineralogical/structural explanation for their remarkable catalytic behavior, while relating them to a natural setting relevant for early Earth geochemistry and prebiotic chemistry.

In the present work, the conversion of bio‐based aldaric acids into muconic and adipic acid through a heterogeneous catalytic process, in the absence of corrosive reagents or gaseous H₂ is reported. The mechanism of the selective removal of adjacent OH* groups on Re/C catalysts and the role of (m)ethanol in carboxylic group protection and hydrogen transfer in a slurry reactor are elucidated by DFT calculations and XPS, chemisorption, and HR‐TEM.

S‐Adenosyl‐L‐methionine (AdoMet) analogs provide a way to study and control methyltransferase target sites. Their enzymatic generation has been limited to aliphatic groups at the sulfur atom. We engineered and crystallized the first SAM synthetases (PC‐MATs) able to generate AdoMet analogs with photocaging groups. In combination with DNA‐MTases, sequence‐specific modification (“writing”) of plasmid DNA and light‐triggered removal (“erasing”) is demonstrated.

A highly active and robust zinc guanidine catalyst for the polymerization of lactide and ϵ‐caprolactone was investigated. The catalyst not only has a faster catalytic activity in bulk for the ring‐opening polymerization of lactide than the industrially used Sn(Oct)₂ catalyst but also leads to a higher degree of crystallinity in the polymer then Sn(Oct)₂, progressing towards a more robust degradation profile.

Electrocatalytic hydrogenation of benzaldehyde to benzyl alcohol on carbon‐supported metals proceeds through proton‐coupled electron transfer. The presence of polar co‐adsorbates such as phenols enhances the hydrogenation rate of the aldehyde by the polarization of the carbonyl group because of the formation of a hydrogen bond. Increasing either the concentration or acidity of the co‐adsorbate increases the rates of selective carbonyl reduction.

Polymersomes with nucleobase pairs in their membrane become transiently permeable for substrates when shear forces are applied. These force‐responsive polymersomes allow to switch on enzymatic reactions by turbulent mixing of vesicle dispersions, which is demonstrated with colorimetric and chemoluminescent reactions, as well as the curing of hydrogels.

The reaction of pentaphosphaferrocene [Cp*Fe(η⁵‐P₅)] with cationic electrophiles results in the formation of the complexes [Cp*Fe(η⁵‐P₅R)][B(C₆F₅)₄] (R=SiEt₃, H, Me). These compounds represent the first structurally characterised coordination complexes bearing elusive pentaphospholes (cyclo‐P₅R) as ligands, including the parent cyclo‐P₅H.

The solvatochromic fluorescence properties of a subporphyrazine are used to control the rate of intramolecular Förster resonance energy transfer (i‐FRET) in a subporphyrazine–pentacene conjugate (SubPzPnc₂) that undergoes intramolecular singlet fission (i‐SF). A simple selection of solvent serves to optimize the triplet quantum yield by enhancing the spectral overlap between the fluorescence of the SubPz and the absorption of the Pnc dimer.

The presence of a nitrile ligand renders cationic group VI metal imido alkylidene NHC complexes air‐stable, functional‐group‐tolerant, and olefin metathesis‐active. No pre‐activation is required and no loss of activity, productivity, or selectivity in olefin metathesis is observed due to the presence of a nitrile ligand.

An air‐stable surface [bipy‐Ru^II(CO)₂Cl₂] single site is designed towards CO oxidation, while all other Ru^III single sites are not active. The methodology is further extended to nine transition‐metal single‐site systems, enabling the use of surface coordination chemistry in heterogeneous catalysis.

Selective H₃O⁺ intercalation is demonstrated for a water‐proton co‐intercalated α‐MoO₃ cathode in a neutral ZnCl₂ electrolyte, thus providing substantially enhanced specific capacity, rate capability, and cycling stability. H₂O molecules between the α‐MoO₃ interlayers are uncovered to block Zn²⁺ intercalation pathways, while allowing smooth H₃O⁺ intercalation/diffusion through a Grotthuss proton conduction mechanism.

Hafnium zeolites are shown to catalyse glucose–fructose isomerisation to thermodynamic equilibrium during continuous operation, which no chemical catalyst has yet been able to achieve. Fructose yields of 58 % are observed at a selectivity of 94 %. Structure–activity relationships are developed with X‐ray absorption spectroscopy, chemisorption FTIR, operando UV/Vis and HSQC NMR spectroscopy.

The photo‐effect on ion conduction in mixed cation and halide perovskites is studied. Unlike A‐site substitution, anion replacement is of great influence. In I‐Br mixtures the differences in hole localization and defect formation favor (reversible) photo‐demixing (the situation in the right part is simplified as the interstitial neutral iodine is further stabilized by ionic rearrangement, and the hole in the bromide is delocalized over several regular anions).

A reaction with the overall appearance of (OCP)⁻ concerted cleavage is revealed to proceed through a [2+2+1]‐cycloaddition reaction intermediate, introducing an unprecedented example of (OCP)⁻ cycloaddition under reducing conditions to the established neutral and oxidative cycloaddition classes of (OCP)⁻ reactivity.

Background

Huntington's disease (HD) develops in individuals with extended cytosine‐adenine‐guanine (CAG) repeats within the huntingtin (HTT) gene, causing neurodegeneration and progressive motor and cognitive symptoms. The inclusion of mutant HTT carriers in whom overt symptoms are not yet fully manifest in therapeutic trials would enable the development of treatments that delay or halt the accumulation of significant disability.

By combining high‐pressure powder X‐ray diffraction and molecular dynamics simulation we gain insight into the microscopic chemical factors that determine the high‐pressure macroscopic thermodynamics of two flexible pillared‐layer MOFs, identifying configurational entropy as originating from side‐chain modifications as the determining factor of the macroscopic thermodynamics.

Change of the excitation wavelength enables formation of interpenetrating polymer networks based on radical and cationic photopolymerization where heptamethines and iodonium salts served as initiating system also for photopolymerization of epoxides, oxetanes and vinyl ether. Engineering of the anion marked the tetra(nonafluoro‐t‐butoxy)aluminate as best candidate.

Gold nanoparticles passivated with Zn(II) complexes and short peptides were transformed into nanozymes able to very efficiently cleave plasmid DNA with a mechanism not much different from that of mononuclear nucleases.

Blue‐light control of the proteasome is achieved using a new photocaging approach. Photolabile protection of the versatile proteasome inhibitor MG132 at the reactive aldehyde function abolished proteasome binding. After irradiation MG132 activity is restored resulting in cell‐cycle arrest at metaphase or apoptosis. This visible‐light‐responsive tool opens up new avenues for spatiotemporal control of the proteasome in basic and medicinal research.

Dynamics in complexes of porphyrin cage compounds and viologen‐derived guest molecules are investigated by selective exchange NMR spectroscopy (1D EXSY). These studies explore the mechanism of host–guest exchange, how steric and electronic properties influence the rate of exchange, and whether the exchange process is governed by kinetic or thermodynamic factors.

The advanced Pd catalyst system with Neolephos as a ligand enables highly selective hydroamidation of unbiased (un)symmetrical 1,3‐diynes. In this way, a wide range of synthetically useful α‐alkynyl‐α,β‐unsaturated amides are afforded in good to high yields with excellent chemo‐, regio‐, and stereoselectivities.

The in situ formation of nucleophilic allylboranes from H₂ and allenes is reported. The reaction is catalyzed by pyridonate borane that displays frustrated‐Lewis‐pair reactivity. The allylboranes that are generated in this way are reactive towards nitriles. Mechanistic investigations show that a change in the binding mode of the pyridonate substituent upon hydrogen activation is essential for the formation of the allylboranes.

Germanane was synthesized by topotatic deintercalation of β‐CaGe2 in aqueous HF solution at room temperature under stirring for 2‐3 minutes. In order to remove the residual CaF₂ the material was treated with a saturated aqueous solution of EDTA.

Nanoassembly can play a key role in generating effective vaccines for emerging (SARS‐CoV‐2) and established (influenza) pandemic threats. SpyTag‐mediated display was used to adapt the nanocage to the challenge of bacterial or viral antigens with diverse cyclic and dihedral symmetries. Establishing display of both trimeric and tetrameric antigens may lead to an influenza vaccine with broader protection.

Total synthesis allowed the identification of the most likely stereostructure of the cytotoxic marine macrolides of the formosalide family (see structure) from eight possibilities. The successful route was based upon an inherently flexible blueprint that builds all stereogenic centers by strictly catalyst controlled transformations prior to formation of the polycyclic framework by late‐stage alkyne metathesis followed by a π‐acid‐catalyzed transannular cyclization

A series of chiral, water‐soluble, DO3A‐based Eu^III complexes was designed and synthesized. The chiral substituents introduced onto the macrocyclic scaffolds enhanced the photophysical properties with quantum yields up to 31 % and |g_lum| up to 0.240. The |g_lum| value increased by 20 % from 0.222 to 0.267 under external magnetic field showing a linear response.

Background

Numerous studies indicate an association between neurodegenerative and metabolic diseases. Although still a matter of debate, growing evidence from epidemiological and animal studies indicate that preexisting diabetes increases the risk to develop Parkinson's disease. However, the mechanisms of such an association are unknown.

A synthetic method to replace carbon atoms of π‐extended systems by dissymmetric phosphorus centers was developed. It allowed to conceive optically active, luminescent phosphapyrenes whose dissymmetric phosphorus atoms could be employed as cornerstone to keep control over the 3D arrangement of molecules

The kinetic resolution of secondary alcohols by fluxionally chiral pyridine catalysts is increasingly selective with increasingly bulky substrates. Detailed kinetic and computational studies show that this is mainly caused by a selective reaction rate acceleration for the major isomer through non‐covalent interactions. More bulky catalysts further increase reaction rate and selectivity.

The degree of attenuation of London dispersion in solution is evaluated. Dispersive interactions were examined with azobenzene probes. The effect on half‐lives for the thermally induced Z to E isomerization in several alkane solvents was determined. The results show only a marginally influence on intramolecular dispersion. In solvents with low surface tension, reduced destabilizing solvent‐solvent interactions increase the half‐life up to 20 %.

A joint experimental and computational approach was used to assess reactivity–stereoselectivity relationships of the bacterial sugar caryophyllose, a rare C12‐monosaccharide, containing a characteristic tetrasubstituted stereocenter. The fundamental insights gained guided the rational design of building blocks for the effective and stereoselective assembly of mycobacterial lipooligosaccharide fragments.

Structural searches from first principles have led to the prediction of solid‐state carbodiimides, guanidinates, and ortho‐nitrido carbonates, the latter introducing the diamond motif into condensed‐matter nitrogen chemistry by high pressure. Some of these novel phases are expected to show potential in terms of photoelectrochemical water splitting and nonlinear optics.

A study of mixed thin films of pentacene and tetracene using ultrafast optical spectroscopy revealed spontaneous fission of a singlet exciton on pentacene, resulting in triplets on both chromophores, with a time constant of 26 ps. In blends containing pentacene fractions exceeding 5 %, the pentacene homofission process outcompetes heterofission because of the endothermicity of the latter.